Proteasome Inhibitor

Tyropeptin A-4 (TP-101) is a potent proteasome inhibitor with the ability to inhibit mammalian 20S proteasome activity. Tyropeptin A-4 exerts its inhibitory effect by binding to the site responsible for trypsin-like activity. Tyropeptin A-4 derivative TP-104 has a 20-fold increase in inhibitory activity over Tyropeptin A. TP-110 specifically inhibits trypsin-like activity without affecting PGPH and trypsin-like activity.

20S Proteasome-IN-6 is a species-selective inhibitor of the Mycobacterium tuberculosis 20S proteasome. 20S Proteasome-IN-6 penetrates the Mycobacterium tuberculosis bacilli, sensitizes the bacteria to nitrosative stress, and reduces the bacterial burden of live Mycobacterium tuberculosis within infected macrophages. 20S Proteasome-IN-6 can be used for tuberculosis research.

Calpain Inhibitor XI is a reversible covalent inhibitor of calpain-1. Calpain Inhibitor XI can be used for the research of neurodegenerative disorders.

FV-162 is a potent, orally active and irreversible proteasome inhibitor. FV-162 exhibits cytotoxic to human myeloma cell lines and primary myeloma cells. FV-162 inhibits tumor growth in a myeloma xenograft mouse model. FV-162 can be used for myeloma research.

Antitrypanosomal agent 15 (compound 26) is an orally active, brain-penetrant, selective inhibitor against Trypanosoma cruzi proteasome, with an _pIC₅₀ of 7.4 and <4 for T. cruzi and human proteasome, respectively. Antitrypanosomal agent 15 has favorable ADME properties and can be used for Chagas disease study.

Anticancer agent 114 is a potent and orally active dipeptide boronic acid ester proteasome inhibitor with an IC₅₀ value of 2.2 nM. Anticancer agent 114 has antiproliferative activity against the RPMI-8226 cells. Anticancer agent 114 can be used in research of multiple myeloma.

20S Proteasome-IN-4 (Compound 7) is a brain-penetrant, parasite-selective, orally active 20S proteasome inhibitor with an IC₅₀ of 6.3 nM against T. b. brucei 20S proteasome. 20S Proteasome-IN-4 can be used for the research of human African trypanosomiasis (HAT).

AK 275, a calpain inhibitor, exhibits neuroprotection activity. AK 275 can be used in the study for central nervous system trauma and ischemia.

Cadmium pyrithione is a metal compound that inhibits protein deubiquitinase activity. Cadmium pyrithione treatment results in significant accumulation of ubiquitinated proteins in cancer cells and primary leukemia cells. Cadmium pyrithione strongly inhibits the activity of proteasome deubiquitinase (such as USP14 and UCHL5), but has a smaller inhibitory effect on 20S proteasome activity. The anticancer activity of Cadmium pyrithione is associated with the induction of apoptosis through caspase activation. Furthermore, Cadmium pyrithione inhibition inhibited proteasome function and suppressed tumor growth in animal xenograft models.

LU-002i TFA is a subunit-selective human proteasome β2c and β2i inhibitor with an IC₅₀ value of 220 nM for β2i.

Sadopeptins B is a nature product that could be isolated from Streptomyces sp. Sadopeptins B is a potent proteasome inhibitor.

TP-110 is a proteasome inhibitor. TP-110 specifically inhibits the protease-like activity of the 20S proteasome, but does not affect the trypsin-like or peptidyl-glutamyl peptide hydrolysis activity. TP-110 inhibits the NF-κB pathway, activates caspase-8, -9, and -3, and causes PARP cleavage, significantly reducing the levels of cIAP-1 and XIAP. TP-110 causes cell cycle arrest at the G2/M phase and promotes apoptosis of cancer cells. TP-110 can be used in cancer research of prostate cancer and multiple myeloma, etc.

Acetyl-Calpastatin(184-210)(human) TFA is a potent, selective and reversible calpain inhibitor with K_i values of 0.2 nM and 6 μM for µ-calpain and cathepsin L, respectively.

TCL1 is a selective non-covalent inhibitor targeting the Pru domain of the Rpn-13 subunit in the 19S regulatory particle (19S RP) of the proteasome with an IC₅₀ value of approximately 26 μM. TCL1 interferes with the recognition and transport of ubiquitinated proteins by Rpn-13, inhibits the degradation of proteins by the proteasome, and thus affects the balance of intracellular protein metabolism. TCL1 is promising for research of hematological malignancies.

ZINC09518833 is a α-ketoamide nonpeptidic proteasome inhibitor with an IC₅₀ value of 12.4 μM. ZINC09518833 binds both primed and nonprimed sites of the proteasome. ZINC09518833 is promising for research of multiple myeloma (MM).

Berberine-amide-m-PhBA chloride (Compound 8b) is a selective anti-breast cancer agent. Berberine-amide-m-PhBA chloride may inhibit the proteasome by interacting with the 20S proteasome β5 subunit. Berberine-amide-m-PhBA chloride can be used in the research of breast cancer.

Celastrol (GMP) (Tripterine (GMP)) is Celastrol (HY-10227) produced by using GMP guidelines. GMP small molecules works appropriately as an auxiliary reagent for cell therapy manufacture. Celastrol (Tripterine;Tripterin) is a proteasome inhibitor which potently and preferentially inhibits the chymotrypsin-like activity of a purified 20S proteasome with IC₅₀ of 2.5 μM. In addition, Celastrol is also an antibiotic with potent antimicrobial activity against standard and clinical methicillin-resistant Staphylococcus aureus (MRSA) strains, inducing oxidative stress and inhibiting DNA synthesis by binding to P5CDH.

CWHM-117 is an orally active aspartic protease inhibitor with selective activity against Toxoplasma gondii. CWHM-117 inhibits the proliferation of Toxoplasma gondii tachyzoites in human fibroblasts, with an EC₅₀ of 2.00 µM. CWHM-117 delays mortality in an acute mouse model of toxoplasmosis. In a chronic mouse model of toxoplasmosis, CWHM-117 reduces brain cyst burden and prolongs survival. CWHM-117 can be used for research on toxoplasmosis.

Argyrin B, a natural product cyclic peptide, is a reversible, non-competitive immunoproteasome inhibitor. Argyrin B shows selective inhibition of the β5i and β1i sites of the immunoproteasome over the β5c and β1c sites of the constitutive proteasome with nearly 20-fold selective inhibition of β1i over the homologous β1c. Argyrin B has antibacterial effects.

Anticancer agent 233 (compound 5g) is a 3,5-bis(arylmethylene)-4-piperidinone derivative with anticancer activity, with GI₅₀ of 0.25 and 0.23 μM for cervical cancer (HeLa) and colon cancer (HCT116) cell lines, respectively. The chlorine atom on the aromatic ring of Anticancer agent 233 interacts well with the catalytic site of 20S proteasome, inhibiting the activity of 20S proteasome to exert its anticancer effect.